Research On Natural Products Based On Ecoadaptability

In the long process of evolution for plants or microbes,it is certain that special chemical components should be produced in response to changes in the surrounding ecological environment and the special chemical components are rich sources of natural products with remarkable bioactivities.Due to plants of the Dipterocarpaceae family living in the tropical regions with strong UV light,and plant diseases and insect pests,the long-term evolution makes them produce resveratrol oligomers with structural diversity and remarkable bioactivities to cope with the challenges,which are increasingly becoming an important source for natural products research.Moreover,plant endophytic fungi living in special habitats and possessing the high mutation probability have been proven to be a new source of bioactive substances with novel skeleton.To deal with many diseases threatening human being,the two biological materials have attracted more and more attention in order to find new lead compounds for drug discovery.In order to mine more natural products with novel structures and bioactivities,their secondary metabolites from the plant Dipterocarpus alatus and the two fungi Diaporthe sp.(IFB-31p-10)and Pleosporales sp.isolated from the plant Rhizophora stylosa and the green algae Rhizophora stylosa,respectively,were investigated in this research.Sixty-seven compounds were isolated through different chromatographic separation techniques including silica gel chromatography,TLC,ODS reversed phase column,sephadex gel chromatography and HPLC.All of the compounds were identified by comprehensive spectrum analysis(HMQC?1H-1H COSY?HMBC?NOESY?ROESY?CD)and X-ray single crystal diffraction including fourty-one new compounds(seven resveratrol polymers,fourteen terpenes,three azaphilones,fourteen tryptamine derivatives,three polyketides).Furthermore,twelve tryptamine derivatives are fully identified as novel skeleton compounds.Finally,the bioactivities of some compounds were evaluated.The details were described as follow:1)Seven unprecedented compounds(1-7)along with nintheen known analogues are characterized from Dipterocarpus alatus,most of which are resveratrol dipolymer,resveratrol tripolymer,resveratrol tripolymer,resveratrol tetramer and glycosides.Compounds 1 and 5 are resveratrol dipolymer derived from the skeleton rearrangement and show moderate inhibitory activity of acetylcholinesterase with IC50 values of 8.28 ?M and 9.11 ?M,respectively.2)Twenty compounds were isolated and identified including five polyketides and fifteen sesquiterpenoids from solid fermentation of Diaporthe sp.IFB-31p-10 residing in Rhizophora stylosa,among which thirteen compounds(27-39)possessed new structures and compound 35 showed cytotoxicity against human colon cancer celline SW480.For sake of structural modification and searching novel compounds through activating slient genes,we obtained fourteen novel tryptamine derivatives by adding tryptamine into the culture of Diaporthe sp.IFB-31p-10,including twelve novel skeleton compounds(47-59).3)Four rare miscellaneous sesquiterpenes and three polyketides were isolated from Pleosporales sp.associated with Enteromorpha clathrata.The MIC values of compound 64 and 65 were 9.48 ?g/ml and 7.44 ?g/ml against Clavibacter michiganense subsp.Sepedonicus and Candida albicans,respectively.Furhermore,Compounds 61-63 exhibited moderate inhibitory activities against the lipopolysaccharide(LPS)-induced intracellular IL-6 production of murine macrophage cell line RAW264.7.Our work indicates that special eco-environment plants or microorganism are the major source of novel biofunctional natural products which enrich structure types and provide leads for drug discovery and optimization.Morever,this thesis summarizes research progress of second metabolites associated with entophytes in recent years.